https://scholars.lib.ntu.edu.tw/handle/123456789/193256
標題: | An Acidic Extracellular Ph Disrupts Adherens Junctions in Hepg2 Cells by Src Kinases-Dependent Modification of E-Cadherin | 作者: | CHEN, CHIA-HUEI TUNG, PO-YUAN HUANG, SHIH-HORNG WANG, SEU-MEI |
關鍵字: | EXTRACELLULAR ACIDIC PH;ADHERENS JUNCTION;E-CADHERIN;p120 CATENIN;c-Src;FYN KINASE | 公開日期: | 2009 | 起(迄)頁: | 851-859 | 來源出版物: | Journal of Cellular Biochemistry | 摘要: | We have previously shown that culturing HepG2 cells in pH 6. 6 culture medium increases the c-Src-dependent tyrosine phosphorylation of beta- catenin and induces disassembly of adherens junctions (AJs). Here, we investigated the upstream mechanism leading to this pH 6.6-induced modification of E- cadherin. In control cells cultured at pH 7.4, E- cadherin staining was linear and continuous at cell-cell contact sites. Culturing cells at pH 6.6 was not cytotoxic, and resulted in weak and discontinuous junctional E-cadherin staining, consistent with the decreased levels of E-cadherin in membrane fractions. pH 6.6 treatment activated c-Src and Fyn kinase and induced tyrosine phosphorylation of p 120 catenin (p120ctn) and E-cadherin. Inhibition of Src family kinases by PP2 attenuated the pH 6.6-induced tyrosine phosphorylation of E-cadherin and p120ctn, and prevented the loss of these proteins from AJs. In addition, E-cadherin was bound to Hakai and ubiquitinated. Furthermore, pH 6.6- induced detachment of E-cadherin from AJs was blocked by pretreatment with MG132 or NH4Cl, indicating the involvement : of ubiquitin-proteasomal/lysosomal degradation of E- cadherin. An early loss of p120ctn prior to E-cadherin detachment from AJs was noted, concomitant with a decreased association between p120ctn and E-cadherin at pH 6.6. PP2 pretreatment prevented the dissociation of these two proteins. In conclusion, pH 6.6 activated Src kinases, resulting in tyrosine phosphorylation of E-cadherin and p120 ctn and a weakening of the association of E-cadherin with p 120ctn and contributing to the instability of E-cadherin at AJs. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/185892 | DOI: | 10.1002/jcb.22313 | SDG/關鍵字: | 4 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; ammonium chloride; benzyloxycarbonylleucylleucylleucinal; catenin; protein kinase Fyn; protein tyrosine kinase; uvomorulin; article; cancer cell culture; cell contact; cell interaction; cell junction; down regulation; enzyme modification; human; human cell; oncogene src; pH measurement; priority journal; protein phosphorylation; Adherens Junctions; Cadherins; Catenins; Cell Membrane; Enzyme Inhibitors; Gene Expression Regulation; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Lysosomes; Phosphorylation; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins c-fyn; src-Family Kinases; Ubiquitin |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。